International Journal of Medical Sciences

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20 April 2019

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Int J Med Sci 2019; 16(1):93-105. doi:10.7150/ijms.29560

Research Paper

Deduction of Novel Genes Potentially Involved in Upper Tract Urothelial Carcinoma Using Next-Generation Sequencing and Bioinformatics Approaches

Hsiang-Ying Lee1,2,3*, Yi-Jen Chen1,4*, Ching-Chia Li2,3,5,6, Wei-Ming Li3,5,6,7, Ya-Ling Hsu6, Hsin-Chih Yeh2,3,5,6, Hung-Lung Ke3,5,6, Chun-Nung Huang2,3,5,6, Chien-Feng Li8, Wen-Jeng Wu2,3,5,6✉, Po-Lin Kuo1,9,10✉

1. Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
2. Department of Urology, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung, Taiwan
3. Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
4. Department of Physical Medicine and Rehabilitation, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
5. Department of Urology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
6. Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
7. Department of Urology, Ministry of Health and Welfare Pingtung Hospital, Pingtung, Taiwan
8. Department of Pathology, Chi Mei Medical Center, Tainan, Taiwan
9. Center for Infectious Disease and Cancer Research, Kaohsiung Medical University, Kaohsiung 807, Taiwan
10. Institute of Medical Science and Technology, National Sun Yat-Sen University, Kaohsiung, Taiwan
*Hsiang-Ying Lee and Yi-Jen Chen contributed equally to this work

Abstract

Upper tract urothelial carcinoma (UTUC) is a relatively uncommon cancer worldwide, however it accounts for approximately 30% of urothelial cancer in the Taiwanese population. The aim of the current study is to identify differential molecular signatures and novel miRNA regulations in UTUC, using next-generation sequencing and bioinformatics approaches. Two pairs of UTUC tumor and non-tumor tissues were collected during surgical resection, and RNAs extracted for deep sequencing. There were 317 differentially expressed genes identified in UTUC tissues, and the systematic bioinformatics analyses indicated dysregulated genes were enriched in biological processes related to aberration in cell cycle and matrisome-related genes. Additionally, 15 candidate genes with potential miRNA-mRNA interactions were identified. Using the clinical outcome prediction database, low expression of SLIT3 was found to be a prognostic predictor of poor survival in urothelial cancer, and a novel miRNA, miR-34a-5p, was a potential regulator of SLIT3, which may infer the potential role of miR-34a-5p-SLIT3 regulation in the altered tumor microenvironment in UTUC. Our findings suggested novel miRNA target with SLIT3 regulation exerts potential prognostic value in UTUC, and future investigation is necessary to explore the role of SLIT3 in the tumor development and progression of UTUC.

Keywords: upper tract urothelial carcinoma, cell cycle, matrisome, next-generation sequencing, bioinformatics

This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license (https://creativecommons.org/licenses/by-nc/4.0/). See http://ivyspring.com/terms for full terms and conditions.
How to cite this article:
Lee HY, Chen YJ, Li CC, Li WM, Hsu YL, Yeh HC, Ke HL, Huang CN, Li CF, Wu WJ, Kuo PL. Deduction of Novel Genes Potentially Involved in Upper Tract Urothelial Carcinoma Using Next-Generation Sequencing and Bioinformatics Approaches. Int J Med Sci 2019; 16(1):93-105. doi:10.7150/ijms.29560. Available from http://www.medsci.org/v16p0093.htm